- |||||||||| fluvastatin / Generic mfg.
Journal: Role of OATP2B1 in drug absorption and drug-drug interactions. (Pubmed Central) - Jul 21, 2021
Although several prescription drugs, including hydroxymethylglutaryl-coenzyme A-CoA reductase inhibitors (statins) such as fluvastatin, are OATP2B1 substrates in vitro, evidence supporting the in vivo relevance of this transporter remains limited, and most has relied on substrate-inhibitor interactions resulting in altered pharmacokinetic properties of the victim drugs...SIGNIFICANCE STATEMENT: The current investigation suggests that OATP2B1-deficient mice provide a valuable tool to study the in vivo importance of this transporter. In addition, our studies have identified novel potent inhibitors of OATP2B1 among the class of tyrosine kinase inhibitors, a rapidly expanding class of drugs used in various therapeutic areas that may cause drug-drug interactions with OATP2B1 substrates.
- |||||||||| cyclosporine / Generic mfg.
Journal: Interferon-γ-induced HLA Class II expression on endothelial cells is decreased by inhibition of mTOR and HMG-CoA reductase. (Pubmed Central) - Jul 11, 2021
Interferon-γ (IFN-γ)-induced HLA class II DR (HLA-DR) was downregulated by everolimus (EVR, 49.1% ± 0.8%; P < 0.01) and fluvastatin (FLU, 33.8% ± 0.6%; P < 0.01)...In contrast, cyclosporine, tacrolimus, mycophenolic acid, and prednisolone did not exhibit any significant suppressive effect...Imaging analysis revealed that HLA-DR expressed in cytosol or on the cell surface was repressed by EVR (cytosol: 58.6% ± 4.9%, p < 0.01; cell surface: 80.9% ± 4.0%, p < 0.01) and FLU (cytosol: 19.0% ± 3.4%, p < 0.01; cell surface: 48.3% ± 4.8%, p < 0.01). These data indicated that FLU and EVR suppressed IFN-γ-induced HLA-DR expression at the transcriptional and post-translational level, respectively, suggesting a potential approach for alleviating DSA-related issues in organ transplantation.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Review, Journal: Hydrophilic or Lipophilic Statins? (Pubmed Central) - Jun 8, 2021
The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity...Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.
- |||||||||| fluvastatin / Generic mfg.
Clinical, Journal: Preadmission Statin Prescription and Inpatient Myocardial Infarction in Geriatric Hip Fracture. (Pubmed Central) - Jun 3, 2021
Statins were not associated with having a non-fatal MI (OR 1.47, 95% CI: 0.58-3.71; p = 0.416) or preventing fatal MI (OR = 0.40, 95% CI: 0.08-1.93; p = 0.255). Preadmission statin use and associations with clinically diagnosed inpatient MI or survival after inpatient MI were not able to be established.
- |||||||||| fluvastatin / Generic mfg.
[VIRTUAL] Extracellular vehicles carrying HIV-1 Nef induce trained immunity in myeloid cells () - May 27, 2021 - Abstract #IASHIV2021IAS_HIV_824;
The mechanisms of this activity seem to be similar to those described for beta-glucan and rely on cholesterol metabolism product mevalonate. Trained immunity may explain enhanced responses of monocytes/macrophages of HIV-infected individuals to inflammatory stimuli and sustained low-level inflammation even when viral load is reduced to undetectable levels.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Review, Journal: Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus. (Pubmed Central) - May 26, 2021
Plasma and serum concentrations of statins were accompanied by alteration in cellular activities including oxidative stress, Akt inhibition, and endothelial nitric oxide synthase (eNOS) and phosphorylation that were reflected in changes in the adverse drug reaction profile of the differing statins. Given that dyslipidemia frequently accompanies diabetes and statin therapy is common, more clinical studies are needed regarding the effects of diabetes on the effectiveness of these drugs.
- |||||||||| Livalo (pitavastatin) / Kowa, Eli Lilly
Journal: Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring. (Pubmed Central) - May 21, 2021
Methods Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested...Results Due to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively...However, nothing was known concerning patients' adherence and time between intake and sampling. Conclusions An LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated.
- |||||||||| fluvastatin / Generic mfg.
[VIRTUAL] Loss of isoprenylation significantly reduces IgE mediated mast cell activation () - May 19, 2021 - Abstract #IMMUNOLOGY2021IMMUNOLOGY_1469;
Repurposing statin drugs such as Fluvastatin as a therapeutic treatment of allergic disease showed reduced allergic symptoms using in vitro and in vivo mouse models...Finally, inhibition of Ras, a known target of prenylation, can mimic statin effects on IgE-mediated mast cell function. These data support the hypothesis that dual farnesyl and geranylgeranyl transferase inhibitors may be an effective therapeutic treatment for mast cell-associated diseases.
- |||||||||| fluvastatin / Generic mfg.
[VIRTUAL] Loss of isoprenylation significantly reduces IgE mediated mast cell activation () - May 19, 2021 - Abstract #IMMUNOLOGY2021IMMUNOLOGY_1175;
Repurposing statin drugs such as Fluvastatin as a therapeutic treatment of allergic disease showed reduced allergic symptoms using in vitro and in vivo mouse models...Finally, inhibition of Ras, a known target of prenylation, can mimic statin effects on IgE-mediated mast cell function. These data support the hypothesis that dual farnesyl and geranylgeranyl transferase inhibitors may be an effective therapeutic treatment for mast cell-associated diseases.
- |||||||||| rifampicin / Generic mfg., fluvastatin / Generic mfg.
Trial completion, Enrollment change: Drug-Drug Interaction Between Rifampin and Fluvastatin (clinicaltrials.gov) - Apr 8, 2021
P4, N=10, Completed,
The validity of NFeO@Zn(GA)/Starch-Hydrogel for removal of FLV statin drug from real water matrices was confirmed in the range 96.15-99.99 %. Recruiting --> Completed | N=20 --> 10
- |||||||||| Triglide (fenofibrate) / Vectura, Shionogi
[VIRTUAL] Statin Intolerance: Prevalence and Management in a Specialized Lipid Clinic () - Mar 27, 2021 - Abstract #ENDO2021ENDO_3210;
Fenofibrate was associated with significantly less frequent adverse effects than statins (p=0.006)...For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
- |||||||||| fluvastatin / Generic mfg.
Review, Journal: Antifungal effects of statins. (Pubmed Central) - Mar 23, 2021
Fluvastatin is considered the most effective statin with the broadest and most potent fungal inhibitory activity, including fungicidal and/or fungistatic properties...Although only a limited number of animal and human studies have been reported to date, observational cohort studies have confirmed that patients using statins have a reduced risk of candidemia-related complications. Further studies are warranted to confirm our findings and expand current knowledge of the anti-fungal effects of statins.
- |||||||||| bortezomib / Generic mfg., fluvastatin / Generic mfg.
Journal: The mevalonate pathway is an actionable vulnerability of t(4;14)-positive multiple myeloma. (Pubmed Central) - Mar 23, 2021
Notably, fluvastatin treatment synergized with bortezomib to induce apoptosis in t(4;14)-positive cells and potentiated the anti-tumor activity of bortezomib in vivo. Our data implicate the t(4;14) translocation as a biomarker of statin sensitivity and warrant further clinical evaluation of a statin in combination with bortezomib for the treatment of t(4;14)-positive disease.
- |||||||||| fluvastatin / Generic mfg.
Journal: Statins Directly Influence the Polarization of Adipose Tissue Macrophages: A Role in Chronic Inflammation. (Pubmed Central) - Mar 7, 2021
Based on modifying the LDL cholesterol concentrations, statins are suggested to decrease the cholesterol inflow through the lipid raft of macrophages in adipose tissue and hypercholesterolemia to enhance the pro-inflammatory macrophage phenotype polarization. On the contrary, due to their opposite effect, statins respond with anti-inflammatory activity, affecting the whole organism.
- |||||||||| atorvastatin / Generic mfg., fluvastatin / Generic mfg.
Journal: Fluvastatin and atorvastatin induce programmed cell death in the brain eating amoeba Naegleria fowleri. (Pubmed Central) - Feb 26, 2021
The obtained results revealed that both statins induced PCD in the treated amoebae after the observation of condensed chromatin, cell membrane damages, mitochondrial membrane potential and ATP levels collapse and ROS generation. In conclusion, both fluvastatin and atorvastatin could be potential new candidates for PAM therapy since they are active at low concentrations, induce low toxicity and cause PCD in the treated amoebae, hence avoiding the activation of inflammation pathways.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg., cyclosporine / Generic mfg.
PK/PD data, Journal: Prediction of Cyclosporin-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Model Characterizing Interplay of Drug Transporters and Enzymes. (Pubmed Central) - Feb 26, 2021
Cyclosporine A (CsA) is an inhibitor of OATPs, P-gp, MRP2, BCRP and CYP3As...We aimed to establish a whole-body physiologically-based pharmacokinetic (PBPK) model which predicts disposition of CsA and nine victim drugs including atorvastatin, cerivastatin, pravastatin, rosuvastatin, fluvastatin, simvastatin, lovastatin, repaglinide and bosentan, as well as drug-drug interactions (DDIs) of CsA with nine victim drugs to investigate the integrated effect of enzymes and transporters in liver, intestinal and kidney on drug disposition...The contributions to atorvastatin disposition were hepatic OATPs > hepatic CYP3A > intestinal CYP3As ≈ efflux transporters (P-gp/BCRP/MRP2). The results got the conclusion that the developed PBPK model characterizing the interplay of enzymes and transporters was successfully applied to predict the pharmacokinetics of 10 OATP substrates and DDIs of CsA with 9 victim drugs.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg.
Biomarker, PK/PD data, Review, Journal: An updated review of pharmacokinetic drug interactions and pharmacogenetics of statins. (Pubmed Central) - Feb 5, 2021
Fluvastatin is metabolized by CYP2C9, whereas pravastatin, rosuvastatin, and pitavastatin are unaffected by inhibition by either CYP...Since recent studies have shown the involvement of drug transporters such as OATP and BCRP as well as CYPs in statin pharmacokinetics, further clinical studies focusing on the drug transporters are necessary. The establishment of biomarkers based on novel mechanisms, such as the leakage of microRNAs into the peripheral blood associated with the muscle toxicity, is important for the early detection of statin side effects.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg.
Journal: Resveratrol for protection against statin toxicity in C2C12 and H9c2 cells. (Pubmed Central) - Jan 8, 2021
Among the five statins tested, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin, simvastatin is the most toxic one...However, such protection was not found in C2C12 cells. This cell type-dependent effect of RSV adds to the complexity in muscle cell toxicity of statins.
- |||||||||| fluvastatin / Generic mfg., rosuvastatin / Generic mfg., AstraZeneca
Clinical, Review, Journal: Statin Intolerance in Clinical Practice. (Pubmed Central) - Jan 8, 2021
Only 78 patients (26%) were confirmed as being complete statin intolerant following a thorough therapeutic effort. The most tolerated statin was rosuvastatin.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg.
[VIRTUAL] Effect of COVID-19 on statin adherence at a rural, independent pharmacy () - Dec 26, 2020 - Abstract #ASHP2020ASHP_3768;
Pharmacy records will be used to identify patients taking one of the following medications: Livalo (pitavastatin), Pravachol (pravastatin), Zocor (simvastatin), Lescol (fluvastatin), Crestor (rosuvastatin), Mevachor (lovastatin), and Lipitor (atorvastatin)...De-identified prescription fill data will be used to calculate PDC for each patient included. The percent change in PDC will be evaluated.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg., clarithromycin / Generic mfg.
Clinical, Review, Journal: Interaction Potential between Clarithromycin and Individual Statins - a Systematic Review. (Pubmed Central) - Dec 20, 2020
In line, a cohort study found concurrent use of clarithromycin and CYP3A4-metabolized statins to be associated with a doubled risk of hospitalisation with rhabdomyolysis or other statin-related adverse events as compared with azithromycin-statin co-administration. If clarithromycin is necessary, we recommend 1) avoiding co-administration with simvastatin, lovastatin or atorvastatin; 2) withholding or dose-reducing pitavastatin; 3) continuing pravastatin therapy with caution, limiting pravastatin dose to 40 mg daily and 4) continuing fluvastatin or rosuvastatin with caution.
- |||||||||| lovastatin / Generic mfg., pravastatin / Generic mfg.
Journal: Statins combined with niacin reduce the risk of peripheral neuropathy. (Pubmed Central) - Dec 19, 2020
Two hydrophilic statins, rosuvastatin and pravastatin, exhibited a similarly weaker association with neuropathy, while no reports of any association of pitavastatin with neuropathy were found...Multiple reports have stated that niacin is no longer beneficial for the management of hyperlipidemia and should be abandoned. However, given the apparent ability of niacin to reduce the risk of neuropathy, perhaps niacin should not be discarded before further studies are performed to provide more in depth information.
- |||||||||| atorvastatin / Generic mfg., fluvastatin / Generic mfg.
Biomarker, Clinical, PK/PD data, Journal: Plasma mevalonic acid exposure as a pharmacodynamic biomarker of fluvastatin/atorvastatin in healthy volunteers. (Pubmed Central) - Dec 18, 2020
The administration of multiple doses of fluvastatin (n = 15) does not alter the values (geometric mean and 95 % CI) of AUC of MVL [72.00 (57.49-90.18) vs 65.57 (51.73-83.12) ng∙h/mL], but reduces AUC [15.33 (11.85-19.83) vs 8.15 (6.18-10.75) ng∙h/mL] by approximately 47 %, whereas single oral dose administration of atorvastatin (n = 15) reduces both AUC [75.79 (65.10-88.24) vs 32.88 (27.05-39.96) ng∙h/mL] and AUC [17.07 (13.87-21.01) vs 7.01 (5.99-8.22) ng∙h/mL] values by approximately 57 % and 59 %, respectively. In conclusion, the data show that the plasma exposure of MVL represents a reliable pharmacodynamic parameter for PK-PD (pharmacokinetic-pharmacodynamic) studies of fluvastatin in multiple doses and atorvastatin in a single dose.
- |||||||||| fluvastatin / Generic mfg.
Journal: Rheumatoid arthritis downregulates the drug transporter OATP1B1: fluvastatin as a probe. (Pubmed Central) - Dec 18, 2020
In conclusion, the data show that the plasma exposure of MVL represents a reliable pharmacodynamic parameter for PK-PD (pharmacokinetic-pharmacodynamic) studies of fluvastatin in multiple doses and atorvastatin in a single dose. The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.
- |||||||||| fluvastatin / Generic mfg.
Journal: Statin therapy and risk of Alzheimer's and age-related neurodegenerative diseases. (Pubmed Central) - Dec 8, 2020
Pathway analysis indicated unique and common profiles associated with risk reduction efficacy. Benefits and risks of statins relative to neurological outcomes should be considered when prescribed for at-risk NDD populations. Common statin activated pathways indicate overarching systems required for risk reduction whereas unique targets could advance a precision medicine approach to prevent neurodegenerative diseases.
- |||||||||| simvastatin / Generic mfg., lovastatin / Generic mfg.
Journal: Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1. (Pubmed Central) - Dec 1, 2020
Furthermore, we found that the expression of PTTG1 was markedly suppressed by lipophilic statins, such as simvastatin, fluvastatin, mevastatin, and lovastatin, but not by hydrophilic pravastatin...Mechanistically, we found that inhibition of PTTG1 expression by simvastatin was reversed by geranylgeranyl pyrophosphate, but not by farnesyl pyrophosphate, suggesting the involvement of geranylgeranyl synthesis in regulating PTTG1 expression. Our results identified statins as novel inhibitors of PTTG1 expression in breast cancer cells and provide mechanistic insights into how simvastatin prevent breast cancer metastasis as observed in recent preclinical and clinical studies.
- |||||||||| dexamethasone / Generic mfg., fluvastatin / Generic mfg.
Journal: Preventive effect of fluvastatin on the development of medication-related osteonecrosis of the jaw. (Pubmed Central) - Dec 1, 2020
Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents...A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site...Bone volume fraction calculated on μ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.
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